Protease-activated receptor 2 deficiency in hematopoietic lineage protects against myocardial infarction through attenuated inflammatory response and fibrosis

• DOI: 10.1016/j.bbrc.2020.03.077
• Publication Date: 2020-03-20T13:16:45Z
• Authors: Pengfei Zuo; Yinghong Zhu; Yongjun Li; Zhi Zuo; Zulong Sheng; Gaoliang Yan; Genshan Ma
• Keywords: Cardiac Fibrosis; Ventricular remodeling; Knockout mouse; Myocardial fibrosis

Ischaemic heart disease is one of the leading causes death. Protease-activated receptor 2 (PAR2) widely expressed within cardiovascular system and known to mediate inflammatory processes in various immunocytes, such as macrophages, mastocytes neutrophils. Here, we investigated whether activating macrophage PAR2 modulates cardiac remodelling a murine model myocardial infarction. Myocardial infarction was produced by permanent ligation left anterior descending coronary artery (LAD) C57BL/6J background wild-type (WT) mice transplanted with bone marrow from WT or knockout (PAR2 KO) mice. Hematopoietic deficiency had improvement ventricular systolic dysfunction dilatation decreased fibrosis deposition remote zone at 1 week after LAD ligation. Inactivation also led less recruitment macrophages myocardium, which accompanied expression pro-inflammatory cytokines. Furthermore, cultured fibroblasts (CFs) were activated showed fibrotic phenotype being co-cultured medium containing PAR2-activating macrophage, enhances interferon-beta (INF-β) expression. The beneficial effects INF-β neutralisation PAR2-deletion ameliorates JAK/STAT3 pathway CFs, might be attributed CF activation. These data suggest that macrophage-derived IFN-β plays crucial role adverse infarction, least part, through PAR2-dependent mechanism.